Optically active chlorohydrins as chiral C3 and C4 building units: Microbial resolution and synthetic applications

Abstract

Production of highly optically active C3 and C4 chlorohydrins was developed by using the bacteria stereoselectively dehalogenating and assimilating the racemic substrate: Pseudomonas sp. and Alcaligenes sp. These bacteria stereoselectively assimilate (RS)-2,3-dichloro-1-propanol (DCP) and (RS)-3-chloro-1,2-propanediol (CPD) followed by microbial preparation of (R)- and (S)-DCP, and (R)- and (S)-CPD with >99% ee. A novel dehalogenating enzyme, halohydrin dehydro-dehalogenase from one of the above strains, Alcaligenes sp. DS-S-7G, was applicable for preparation of optically active 1,2-diols with 60–99% ee. Moreover, microbial resolution of C4 chlorohydrins with whole cells of Pseudomonas sp. was carried out. This resolution reaction using the resting cells gave (R)- and (S)-4-chloro-3-hydroxybutyrate (CHB) and (S)-4-chloro-3-hydroxybutyronitrile (BN) with >98% ee. In the case of the resting cells of Enterobacter sp., both (R)-CHB (>99% ee) and (S)-3-hydroxy-γ-butyrolactone (95% ee) with excellent yield were obtained. Also, some typical synthetic applications using the above chiral C3 and C4 synthons were introduced: ferroelectric liquid crystals, optically active β-blockers, and other chiral pharmaceuticals. Chirality 10:682–692, 1998. © 1998 Wiley-Liss, Inc.